[A new drug in a new role: dipyridamole in the treatment of HIV-1 infections?].

Dipyridamole (DP) is a widely used coronary vasodilator and antithrombotic drug. The presented experiments demonstrate that DP inhibits the replication of HIV-1 and markedly potentiates the anti-HIV activity of azidothymidine (AZT) and dideoxycytidine in CD4-positive cells (monocyte-macrophages and T-lymphocytes). At the same time DP does not potentiate the bone marrow toxicity of AZT, and, in CEM-ss lymphoblastoid cells, it significantly suppresses the cytotoxicity of AZT. Studies on the mechanism of these effects suggest that DP inhibits the intracellular phosphorylation of physiological nucleosides, whereas it does not affect phosphorylation of AZT and other antiviral dideoxynucleoside drugs. This may lead to relative enhancement of the metabolic activation of dideoxynucleoside drugs and the inhibitory action of their active, triphosphate form on HIV reverse transcriptase. Studies comparing the binding of DP to proteins in tissue culture media and in human plasma suggest that in order to achieve significant antiviral potentiation in vivo, high doses of DP will be required.